CN100467476C - 支化链亲脂性分子衍生物及其用途 - Google Patents
支化链亲脂性分子衍生物及其用途 Download PDFInfo
- Publication number
- CN100467476C CN100467476C CNB01816806XA CN01816806A CN100467476C CN 100467476 C CN100467476 C CN 100467476C CN B01816806X A CNB01816806X A CN B01816806XA CN 01816806 A CN01816806 A CN 01816806A CN 100467476 C CN100467476 C CN 100467476C
- Authority
- CN
- China
- Prior art keywords
- compound
- oxygen base
- purposes
- phosphoric acid
- ethyl ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000002634 lipophilic molecules Chemical class 0.000 title abstract description 12
- 230000004888 barrier function Effects 0.000 claims abstract description 49
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims description 125
- 229910052760 oxygen Inorganic materials 0.000 claims description 82
- 239000001301 oxygen Substances 0.000 claims description 82
- 239000011734 sodium Substances 0.000 claims description 82
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 73
- 206010028980 Neoplasm Diseases 0.000 claims description 65
- 239000003814 drug Substances 0.000 claims description 43
- 230000035699 permeability Effects 0.000 claims description 39
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 36
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 32
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 claims description 31
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 claims description 31
- 210000004556 brain Anatomy 0.000 claims description 29
- -1 4-hexadecyl phosphorylcholine Chemical compound 0.000 claims description 25
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
- 125000004494 ethyl ester group Chemical group 0.000 claims description 21
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 20
- 229960001231 choline Drugs 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- 238000009825 accumulation Methods 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 210000000056 organ Anatomy 0.000 claims description 15
- GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical compound CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 claims description 14
- 229950004354 phosphorylcholine Drugs 0.000 claims description 14
- PYJNAPOPMIJKJZ-UHFFFAOYSA-N phosphorylcholine chloride Chemical compound [Cl-].C[N+](C)(C)CCOP(O)(O)=O PYJNAPOPMIJKJZ-UHFFFAOYSA-N 0.000 claims description 14
- 229910052708 sodium Inorganic materials 0.000 claims description 14
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 13
- 125000004423 acyloxy group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 13
- 230000001225 therapeutic effect Effects 0.000 claims description 13
- 239000013543 active substance Substances 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Substances OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 230000004378 blood-retinal barrier Effects 0.000 claims description 9
- 210000003169 central nervous system Anatomy 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 229940038384 octadecane Drugs 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- 230000003211 malignant effect Effects 0.000 claims description 7
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000001361 intraarterial administration Methods 0.000 claims description 6
- 210000003491 skin Anatomy 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 5
- 210000001508 eye Anatomy 0.000 claims description 5
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 5
- YWOIMIFPWICXIL-UHFFFAOYSA-N CCCCCCCC(OP(O)(O)=O)CCCCCCC Chemical compound CCCCCCCC(OP(O)(O)=O)CCCCCCC YWOIMIFPWICXIL-UHFFFAOYSA-N 0.000 claims description 4
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 238000011275 oncology therapy Methods 0.000 claims description 4
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- 206010058202 Cystoid macular oedema Diseases 0.000 claims description 3
- KGWDUNBJIMUFAP-KVVVOXFISA-N Ethanolamine Oleate Chemical compound NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O KGWDUNBJIMUFAP-KVVVOXFISA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 208000001344 Macular Edema Diseases 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- 239000003429 antifungal agent Substances 0.000 claims description 3
- 208000015114 central nervous system disease Diseases 0.000 claims description 3
- 201000010206 cystoid macular edema Diseases 0.000 claims description 3
- 210000004907 gland Anatomy 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 210000001331 nose Anatomy 0.000 claims description 3
- 230000010412 perfusion Effects 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- 210000001550 testis Anatomy 0.000 claims description 3
- 241000792859 Enema Species 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 201000000582 Retinoblastoma Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 229940034982 antineoplastic agent Drugs 0.000 claims description 2
- 239000003443 antiviral agent Substances 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 239000003139 biocide Substances 0.000 claims description 2
- 210000002937 blood-testis barrier Anatomy 0.000 claims description 2
- 210000000621 bronchi Anatomy 0.000 claims description 2
- 210000003467 cheek Anatomy 0.000 claims description 2
- 210000000795 conjunctiva Anatomy 0.000 claims description 2
- 210000004087 cornea Anatomy 0.000 claims description 2
- 239000007920 enema Substances 0.000 claims description 2
- 229940095399 enema Drugs 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 208000002780 macular degeneration Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 230000000324 neuroprotective effect Effects 0.000 claims description 2
- 208000011581 secondary neoplasm Diseases 0.000 claims description 2
- 210000000278 spinal cord Anatomy 0.000 claims description 2
- 210000001215 vagina Anatomy 0.000 claims description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 claims 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 239000000890 drug combination Substances 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000012049 topical pharmaceutical composition Substances 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 57
- 230000008499 blood brain barrier function Effects 0.000 description 52
- 210000004027 cell Anatomy 0.000 description 50
- 238000000034 method Methods 0.000 description 46
- 238000012360 testing method Methods 0.000 description 39
- 241000700159 Rattus Species 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- 210000001519 tissue Anatomy 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 20
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical class O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 230000002490 cerebral effect Effects 0.000 description 15
- 230000035508 accumulation Effects 0.000 description 14
- 229960002143 fluorescein Drugs 0.000 description 14
- 150000002632 lipids Chemical class 0.000 description 13
- 230000001988 toxicity Effects 0.000 description 13
- 231100000419 toxicity Toxicity 0.000 description 13
- 239000000463 material Substances 0.000 description 12
- 238000011160 research Methods 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 231100000636 lethal dose Toxicity 0.000 description 11
- 238000012544 monitoring process Methods 0.000 description 11
- 230000000149 penetrating effect Effects 0.000 description 11
- 230000000259 anti-tumor effect Effects 0.000 description 10
- DTGKSKDOIYIVQL-NQMVMOMDSA-N (+)-Borneol Natural products C1C[C@]2(C)[C@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-NQMVMOMDSA-N 0.000 description 9
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 9
- 240000005636 Dryobalanops aromatica Species 0.000 description 9
- 241001062009 Indigofera Species 0.000 description 9
- 229960000846 camphor Drugs 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 8
- 210000002919 epithelial cell Anatomy 0.000 description 8
- 238000011081 inoculation Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 229930195725 Mannitol Natural products 0.000 description 7
- 150000001298 alcohols Chemical group 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 239000000594 mannitol Substances 0.000 description 7
- 235000010355 mannitol Nutrition 0.000 description 7
- 239000000700 radioactive tracer Substances 0.000 description 7
- 210000001525 retina Anatomy 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000012453 sprague-dawley rat model Methods 0.000 description 7
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 102000009027 Albumins Human genes 0.000 description 6
- 108010088751 Albumins Proteins 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- 102000003952 Caspase 3 Human genes 0.000 description 5
- 108090000397 Caspase 3 Proteins 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 210000000269 carotid artery external Anatomy 0.000 description 5
- 230000001472 cytotoxic effect Effects 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- NJNWCIAPVGRBHO-UHFFFAOYSA-N 2-hydroxyethyl-dimethyl-[(oxo-$l^{5}-phosphanylidyne)methyl]azanium Chemical group OCC[N+](C)(C)C#P=O NJNWCIAPVGRBHO-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000002146 bilateral effect Effects 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 210000000981 epithelium Anatomy 0.000 description 4
- 208000002409 gliosarcoma Diseases 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000004043 dyeing Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 229960003699 evans blue Drugs 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 3
- 229960003775 miltefosine Drugs 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- 238000012207 quantitative assay Methods 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- LHADAIATWWYJSL-UHFFFAOYSA-N C(C=1C(C(=O)OC2=CC=CC=C2)=CC=CC1)(=O)OC1=CC=CC=C1.P(Cl)(Cl)Cl Chemical compound C(C=1C(C(=O)OC2=CC=CC=C2)=CC=CC1)(=O)OC1=CC=CC=C1.P(Cl)(Cl)Cl LHADAIATWWYJSL-UHFFFAOYSA-N 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 2
- 108010076667 Caspases Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 101800004637 Communis Proteins 0.000 description 2
- 101710112752 Cytotoxin Proteins 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 2
- 235000000177 Indigofera tinctoria Nutrition 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 206010000269 abscess Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000003636 chemical group Chemical group 0.000 description 2
- 201000010989 colorectal carcinoma Diseases 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 239000006059 cover glass Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 239000002619 cytotoxin Substances 0.000 description 2
- 238000013016 damping Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- JIMMILCKVYOFET-UHFFFAOYSA-N hexadecan-4-ol Chemical compound CCCCCCCCCCCCC(O)CCC JIMMILCKVYOFET-UHFFFAOYSA-N 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229940097275 indigo Drugs 0.000 description 2
- COHYTHOBJLSHDF-UHFFFAOYSA-N indigo powder Natural products N1C2=CC=CC=C2C(=O)C1=C1C(=O)C2=CC=CC=C2N1 COHYTHOBJLSHDF-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 208000018389 neoplasm of cerebral hemisphere Diseases 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000001210 retinal vessel Anatomy 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Natural products CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000003104 tissue culture media Substances 0.000 description 2
- 231100000167 toxic agent Toxicity 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 229960000604 valproic acid Drugs 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- UOGZWWISWPADQM-SDVXZCCESA-N (1r,2r,3r,4s,6s)-2,3,6-trichloro-4,7-bis(dichloromethyl)-7-methylbicyclo[2.2.1]heptane Chemical compound Cl[C@H]1C[C@@]2(C(Cl)Cl)[C@@H](Cl)[C@H](Cl)[C@@H]1C2(C(Cl)Cl)C UOGZWWISWPADQM-SDVXZCCESA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 241001269238 Data Species 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241001125671 Eretmochelys imbricata Species 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 101710154643 Filamentous hemagglutinin Proteins 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 206010020852 Hypertonia Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229920002858 MOWIOL ® 4-88 Polymers 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 208000001738 Nervous System Trauma Diseases 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- BDKZHNJTLHOSDW-UHFFFAOYSA-N [Na].CC(O)=O Chemical compound [Na].CC(O)=O BDKZHNJTLHOSDW-UHFFFAOYSA-N 0.000 description 1
- LPQOADBMXVRBNX-UHFFFAOYSA-N ac1ldcw0 Chemical compound Cl.C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3CCSC1=C32 LPQOADBMXVRBNX-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 239000003366 bradykinin receptor agonist Substances 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003059 ependyma Anatomy 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000007684 eye toxicity Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940127021 low-dose drug Drugs 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000028412 nervous system injury Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 231100000327 ocular toxicity Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- FXPDGSSSQUFIPW-UHFFFAOYSA-N oxaphospholane Chemical compound C1COPC1 FXPDGSSSQUFIPW-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 229940061584 phosphoramidic acid Drugs 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 235000019353 potassium silicate Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940056501 technetium 99m Drugs 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 230000003868 tissue accumulation Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000048 toxicity data Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- PZYFJWVGRGEWGO-UHFFFAOYSA-N trisodium;hydrogen peroxide;trioxido(oxo)vanadium Chemical compound [Na+].[Na+].[Na+].OO.OO.OO.[O-][V]([O-])([O-])=O PZYFJWVGRGEWGO-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/11—Esters of phosphoric acids with hydroxyalkyl compounds without further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Neurosurgery (AREA)
- Communicable Diseases (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Virology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Fats And Perfumes (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL13767200A IL137672A0 (en) | 2000-08-03 | 2000-08-03 | Derivatives of branched-chain lipophilic molecules and uses thereof |
| IL137672 | 2000-08-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1633440A CN1633440A (zh) | 2005-06-29 |
| CN100467476C true CN100467476C (zh) | 2009-03-11 |
Family
ID=11074480
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB01816806XA Expired - Fee Related CN100467476C (zh) | 2000-08-03 | 2001-08-01 | 支化链亲脂性分子衍生物及其用途 |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US7186703B2 (xx) |
| EP (1) | EP1305322B1 (xx) |
| JP (1) | JP2004505898A (xx) |
| KR (1) | KR100801207B1 (xx) |
| CN (1) | CN100467476C (xx) |
| AT (1) | ATE455120T1 (xx) |
| AU (2) | AU8004301A (xx) |
| BR (1) | BR0112835A (xx) |
| CA (1) | CA2416808C (xx) |
| CZ (1) | CZ2003208A3 (xx) |
| DE (1) | DE60141074D1 (xx) |
| ES (1) | ES2338987T3 (xx) |
| HU (1) | HUP0301711A3 (xx) |
| IL (1) | IL137672A0 (xx) |
| NZ (1) | NZ523664A (xx) |
| WO (1) | WO2002011666A2 (xx) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7582678B2 (en) | 1997-07-09 | 2009-09-01 | D-Pharm Limited | Use of branched-chain fatty acids and derivatives thereof for the treatment of pain |
| US6518311B2 (en) * | 1997-07-09 | 2003-02-11 | D-Pharm Ltd. | Use of branched-chain fatty acids and derivatives thereof for the treatment of pain |
| DE60125420T2 (de) | 2000-10-10 | 2007-09-27 | University Of North Carolina At Chapel Hill | Zusammensetzungen enthaltend phospholipase c inhibitoren und verfahren zur erhöhung parazellulärer permeabilität der epithelbarriere und endothelbarriere |
| WO2003068242A1 (en) | 2002-02-11 | 2003-08-21 | Vertex Pharmaceuticals Incorporated | Phospholipids as caspase inhibitor prodrugs |
| ES2397060T3 (es) | 2002-04-18 | 2013-03-04 | Opko Pharmaceuticals, Llc | Medios y métodos para la modulación específica de genes diana en el ojo |
| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| WO2006128055A2 (en) * | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Novel phosphorus-containing thyromimetics |
| WO2005051298A2 (en) | 2003-11-19 | 2005-06-09 | Metabasis Therapeutics, Inc. | Novel phosphorus-containing thyromimetics |
| US8153435B1 (en) | 2005-03-30 | 2012-04-10 | Tracer Detection Technology Corp. | Methods and articles for identifying objects using encapsulated perfluorocarbon tracers |
| US20090232879A1 (en) | 2005-05-26 | 2009-09-17 | Metabasis Therapeutics, Inc. | Thyromimetics for the Treatment of Fatty Liver Diseases |
| US8703179B2 (en) * | 2006-05-11 | 2014-04-22 | Kimberly-Clark Worldwide, Inc. | Mucosal formulation |
| EP2180788B1 (en) * | 2007-08-10 | 2016-12-21 | Basil Rigas | Anti-inflammatory compounds and uses thereof |
| US20110158969A1 (en) * | 2008-02-28 | 2011-06-30 | Henry Ford Health System | Compositions and methods for using stromal cells to enhance treatment of central nervous system injuries |
| US20100240883A1 (en) * | 2009-03-18 | 2010-09-23 | Nian Wu | Lipid-drug conjugates for drug delivery |
| JP5853869B2 (ja) * | 2012-06-07 | 2016-02-09 | 日油株式会社 | ホスホリルコリン基含有化合物及びその製造法 |
| CN110198719A (zh) | 2016-11-21 | 2019-09-03 | 维京治疗公司 | 治疗糖原贮积病的方法 |
| AU2018280118B2 (en) | 2017-06-05 | 2021-07-15 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis |
| CA3094167A1 (en) | 2018-03-22 | 2019-09-26 | Viking Therapeutics, Inc. | Crystalline forms and methods of producing crystalline forms of a compound |
| JP2022510691A (ja) | 2018-12-05 | 2022-01-27 | バイキング・セラピューティクス・インコーポレイテッド | 線維症及び炎症の処置のための組成物 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3006946A (en) * | 1953-03-04 | 1961-10-31 | Union Carbide Corp | Production of heterocyclic phosphoruscontaining compounds and products |
| US3260688A (en) | 1962-08-10 | 1966-07-12 | Toyo Koatsu Ind Inc | Resin compositions for producing cellular masses and process for producing a cellular product |
| US3260668A (en) * | 1964-11-04 | 1966-07-12 | Dow Chemical Co | Alkaline scale control in saline water conversion equipment |
| DE2038829C3 (de) * | 1970-08-05 | 1975-11-13 | Chemische Werke Huels Ag, 4370 Marl | Zusatzmittel zu Mörtel oder Beton auf Zementbasis |
| LU65735A1 (xx) | 1972-07-17 | 1974-01-28 | ||
| DE2930756A1 (de) | 1979-07-28 | 1981-02-26 | Cassella Ag | Klotzhilfsmittel und verfahren zum faerben von cellulosefasern bzw. gemischen von cellulosefasern zusammen mit synthesefasern mit schwefel-, schwefelkuepen-, kuepen- und reaktivfarbstoffen |
| JPS6038363B2 (ja) * | 1979-11-27 | 1985-08-31 | ライオン株式会社 | ヘアリンス剤 |
| JPS5716064A (en) * | 1980-07-04 | 1982-01-27 | Dai Ichi Kogyo Seiyaku Co Ltd | Dye dispersion |
| JPS57112317A (en) * | 1980-12-29 | 1982-07-13 | Lion Corp | Hairdressing agent composition |
| JPS5984824A (ja) * | 1982-11-08 | 1984-05-16 | Takeda Chem Ind Ltd | 抗腫瘍剤 |
| JPS6072829A (ja) * | 1983-09-29 | 1985-04-24 | Kao Corp | ベシクル用組成物 |
| JPS60184092A (ja) * | 1984-03-01 | 1985-09-19 | Kao Corp | リン酸エステルおよびその製法 |
| JPH0832832B2 (ja) * | 1984-03-09 | 1996-03-29 | 花王株式会社 | 加熱瀝青質用添加剤 |
| US4670575A (en) | 1984-06-05 | 1987-06-02 | Kao Corporation | Process for purification of phosphoric mono esters |
| JPS61129189A (ja) * | 1984-11-28 | 1986-06-17 | Kao Corp | リン酸エステルまたはその塩の精製方法 |
| US4736051A (en) * | 1985-03-20 | 1988-04-05 | Kao Corporation | Process for the preparation of an alkali metal salt of a diester phosphoric acid |
| US4751320A (en) * | 1985-11-27 | 1988-06-14 | Kao Corporation | Phosphoric ester and process for producing same |
| US5916884A (en) * | 1985-12-04 | 1999-06-29 | Max-Planck-Gesellschaft Zur Foederung Der Wissenschaften | Compositions containing a mixture of phosphorus compounds and alkylglycerols |
| IE59778B1 (en) | 1985-12-04 | 1994-04-06 | Max Planck Gesellschaft | Medicament with anti-tumour action containing hexadecylphosphocholine |
| JPS62177008A (ja) * | 1986-01-29 | 1987-08-03 | Kao Corp | 共重合体の製造法 |
| JPS63122775A (ja) | 1986-11-12 | 1988-05-26 | Kao Corp | 油ゲル化剤 |
| WO1989011299A1 (en) | 1988-05-18 | 1989-11-30 | State Of Oregon Acting By And Through The State Bo | Method for delivery of therapeutic agents to target brain tissue using monoclonal antibody conjugates |
| JPH01290604A (ja) * | 1988-05-18 | 1989-11-22 | Dai Ichi Kogyo Seiyaku Co Ltd | 水中崩壊性良好な農薬粒剤 |
| US5059415A (en) | 1989-02-21 | 1991-10-22 | The State Of Oregon Acting By And Through The Oregon State Board Of Higher Education On Behalf Of Oregon Health | Method for diagnostically imaging lesions in the brain inside a blood-brain barrier |
| FR2677360B1 (fr) * | 1991-06-05 | 1995-04-14 | Atta | Composes amphiphiles perfluoroalkyles du phosphore, leurs preparations et leurs applications notamment dans le domaine biomedical. |
| US5846516A (en) * | 1992-06-03 | 1998-12-08 | Alliance Pharmaceutial Corp. | Perfluoroalkylated amphiphilic phosphorus compounds: preparation and biomedical applications |
| JP2710900B2 (ja) * | 1992-09-02 | 1998-02-10 | 株式会社ディ・ディ・エス研究所 | 酸性官能基を有する脂質誘導体及び同誘導体によって被覆された微粒子キャリヤー |
| US5491004A (en) * | 1994-05-26 | 1996-02-13 | Henkel Corporation | Process for applying a low soiling fiber finish |
| US5686540A (en) * | 1995-09-29 | 1997-11-11 | Dainippon Ink And Chemicals, Inc. | Process for the preparation of lactic acid-based polyester |
| JP3747091B2 (ja) * | 1996-03-22 | 2006-02-22 | 株式会社クラブコスメチックス | アポトーシス誘導剤 |
| US6030961A (en) | 1997-03-11 | 2000-02-29 | Bar-Ilan Research & Development Co., Ltd. | Oxyalkylene phosphate compounds and uses thereof |
| ZA984837B (en) * | 1997-06-04 | 1999-06-04 | Biocompatibles Ltd | Phosphate compounds |
| WO1998055533A1 (en) * | 1997-06-04 | 1998-12-10 | Biocompatibles Limited | Zwitterionic compounds and their use to cross-link collagenous materials |
| IL121268A0 (en) * | 1997-07-09 | 1998-01-04 | Dpharm Ltd | Branched chain fatty acids their derivatives and use in the treatment of central nervous system disorders |
| IL121269A0 (en) * | 1997-07-09 | 1998-01-04 | Dpharm Ltd | Compositions and methods for reversibly increasing permeability of biomembranes |
| JP2000053897A (ja) * | 1998-08-07 | 2000-02-22 | Kao Corp | インクジェット記録用水系インク |
-
2000
- 2000-08-03 IL IL13767200A patent/IL137672A0/xx unknown
-
2001
- 2001-08-01 US US10/343,105 patent/US7186703B2/en not_active Expired - Lifetime
- 2001-08-01 CA CA2416808A patent/CA2416808C/en not_active Expired - Fee Related
- 2001-08-01 BR BR0112835-3A patent/BR0112835A/pt not_active IP Right Cessation
- 2001-08-01 WO PCT/IL2001/000713 patent/WO2002011666A2/en active IP Right Grant
- 2001-08-01 KR KR1020037001485A patent/KR100801207B1/ko not_active IP Right Cessation
- 2001-08-01 EP EP01958325A patent/EP1305322B1/en not_active Expired - Lifetime
- 2001-08-01 AU AU8004301A patent/AU8004301A/xx active Pending
- 2001-08-01 HU HU0301711A patent/HUP0301711A3/hu unknown
- 2001-08-01 NZ NZ523664A patent/NZ523664A/en not_active IP Right Cessation
- 2001-08-01 CZ CZ2003208A patent/CZ2003208A3/cs unknown
- 2001-08-01 ES ES01958325T patent/ES2338987T3/es not_active Expired - Lifetime
- 2001-08-01 JP JP2002517004A patent/JP2004505898A/ja active Pending
- 2001-08-01 AT AT01958325T patent/ATE455120T1/de not_active IP Right Cessation
- 2001-08-01 DE DE60141074T patent/DE60141074D1/de not_active Expired - Lifetime
- 2001-08-01 CN CNB01816806XA patent/CN100467476C/zh not_active Expired - Fee Related
- 2001-08-01 AU AU2001280043A patent/AU2001280043B2/en not_active Ceased
-
2007
- 2007-01-11 US US11/652,309 patent/US7687483B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20070135381A1 (en) | 2007-06-14 |
| NZ523664A (en) | 2004-07-30 |
| US7687483B2 (en) | 2010-03-30 |
| HUP0301711A3 (en) | 2007-05-29 |
| KR20030024823A (ko) | 2003-03-26 |
| HUP0301711A2 (hu) | 2003-09-29 |
| JP2004505898A (ja) | 2004-02-26 |
| AU8004301A (en) | 2002-02-18 |
| IL137672A0 (en) | 2001-10-31 |
| AU2001280043B8 (en) | 2002-02-18 |
| CN1633440A (zh) | 2005-06-29 |
| AU2001280043B2 (en) | 2007-05-24 |
| EP1305322A2 (en) | 2003-05-02 |
| BR0112835A (pt) | 2003-10-21 |
| WO2002011666A2 (en) | 2002-02-14 |
| CZ2003208A3 (cs) | 2003-10-15 |
| EP1305322A4 (en) | 2005-04-13 |
| CA2416808A1 (en) | 2002-02-14 |
| ATE455120T1 (de) | 2010-01-15 |
| CA2416808C (en) | 2011-11-22 |
| EP1305322B1 (en) | 2010-01-13 |
| US7186703B2 (en) | 2007-03-06 |
| KR100801207B1 (ko) | 2008-02-05 |
| WO2002011666A3 (en) | 2002-07-11 |
| DE60141074D1 (de) | 2010-03-04 |
| ES2338987T3 (es) | 2010-05-14 |
| US20030186897A1 (en) | 2003-10-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100467476C (zh) | 支化链亲脂性分子衍生物及其用途 | |
| DE60214134T2 (de) | Modifizierte psma-liganden und deren verwendung | |
| RU2235727C2 (ru) | Растворимые в воде фосфонооксиметиловые эфиры затрудненных спиртов или фенолов, фармацевтические композиции на их основе, способ анестезии и способ лечения опухолевых заболеваний | |
| TW319763B (xx) | ||
| Elliott et al. | Intravenous RMP-7 selectively increases uptake of carboplatin into rat brain tumors | |
| CN105452265B (zh) | 用于治疗肿瘤性疾病尤其具有高her2蛋白水平的肿瘤性疾病的他莫昔芬衍生物 | |
| CN102977360B (zh) | 三苯基膦-聚乙二醇1000维生素e琥珀酸酯共轭化合物及其制备方法与应用 | |
| KR20110018897A (ko) | 수용성 아세트아미노펜 유사체 | |
| CN103221373A (zh) | 用于治疗肺癌的方法和组合物 | |
| CN108430520A (zh) | 长效钆基肿瘤靶向成像与治疗剂 | |
| WO2007112100A2 (en) | Highly fluorinated oils and surfactants and methods of making and using same | |
| KR20070028312A (ko) | 교란된 막에 결합하는 화합물 및 그 이용 방법 | |
| AU2001280043A1 (en) | Derivatives of branched-chain lipophilic molecules and uses thereof | |
| CN105233298A (zh) | 一种紫杉醇类磷脂化合物、其药物组合物及应用 | |
| CN104800828A (zh) | 用于治疗癌症的有机砷化合物和方法 | |
| Davis et al. | Vascular disease in infective endocarditis: report of immune-mediated events in skin and brain | |
| CN101808644A (zh) | 聚合酶抑制剂及其用于治疗肿瘤的应用 | |
| CN103284982A (zh) | 用于治疗癌症转移的方法和组合物 | |
| CN107929262A (zh) | 乙二胺阳离子化白蛋白抗肿瘤纳米粒及其制备方法和用途 | |
| JP5956533B2 (ja) | 放射ターゲット薬物調製用キット及び放射ターゲット薬物の調製方法及び用途 | |
| JPH05505624A (ja) | ラジオグラフィ造影剤として有用なヘキサデンテートリガンド類 | |
| US9119874B2 (en) | Cell-penetrating markers of apoptosis | |
| Basler et al. | Coccidioidomycosis: clinical review and treatment update. | |
| CN103948577A (zh) | 化合物在制备用于治疗、减缓或处理骨癌疼痛的组成物的用途 | |
| White | New Organic Mercurials and Their Therapeutic Applications. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090311 Termination date: 20120801 |